874290-99-0Relevant articles and documents
PYRROLO [2, 3-B] PYRIDINES OR PYRROLO [2, 3-B] PYRAZINES AS HPK1 INHIBITOR AND THE USE THEREOF
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Paragraph 0401; 0898-0900, (2020/01/08)
Disclosed herein is a compound of Formula (AIII) or (III), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.
Discovery of AZD3147: A potent, selective dual inhibitor of mTORC1 and mTORC2
Pike, Kurt G.,Morris, Jeff,Ruston, Linette,Pass, Sarah L.,Greenwood, Ryan,Williams, Emma J.,Demeritt, Julie,Culshaw, Janet D.,Gill, Kristy,Pass, Martin,Finlay, M. Raymond V.,Good, Catherine J.,Roberts, Craig A.,Currie, Gordon S.,Blades, Kevin,Eden, Jonathan M.,Pearson, Stuart E.
, p. 2326 - 2349 (2015/03/30)
High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identifying compounds with improved cellular potency, improved aqueous solubility, and good stability in human hepatocyte incubations. Knowledge from empirical SAR investigations was combined with an understanding of the molecular interactions in the crystal lattice to improve both cellular potency and solubility, and the composite parameters of LLE and pIC50-pSolubility were used to assess compound quality and progress. Predictive models were employed to efficiently mine the attractive chemical space identified resulting in the discovery of 42 (AZD3147), an extremely potent and selective dual inhibitor of mTORC1 and mTORC2 with physicochemical and pharmacokinetic properties suitable for development as a potential clinical candidate.
5,6,7,8-TETRAHYDROPYRIDO[3,4-D]PYRIMIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
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Page/Page column 48, (2010/11/04)
A compound of the Formula I: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
